A,/3-Unsaturated tosylhydrazones

When ot, 3-unsaturated aldehydes were employed, vinylepoxides were obtained with excellent transxis ratios but in poor yields. When benzaldehyde was treated with a, 3-unsaturated tosylhydrazone salts, the yields of vinylepoxides were improved but the transxis ratios dropped. When chiral sulfides were utilized, the ees were high with a, 3-unsaturated aldehydes, whereas unsaturated, chiral sulfur ylides gave moderate ees, poor yields, and modest transxis ratios. 

NaBH3CN, or bis(triphenylphosphine)copper(I) tetrahydroborate.531 The reduction of a, (3-unsaturated tosylhydrazones with NaBH3CN, with NaBH -HOAc, or with catecholborane proceeds with migration of the double bond to the position formerly occupied by the carbonyl carbon, even if this removes the double bond from conjugation with an aromatic ring,532 e.g.. 

Synthesis.—Catecholborane offers a number of advantages over other boron hydrides for the reduction of a)3-unsaturated tosylhydrazones (1) to olefins. Only one equivalent of hydride is used and the conditions are mild. No alkane formation is observed. A study of the isomeric pulegone tosylhydrazones (2) and (3) and the... 

It has been pointed out °° that caution should be exercised in planning alkene syntheses through the reduction of a/3-unsaturated tosylhydrazones with sodium cyanoborohydride. Alkene (imminium ion reduction) and alkane (Michael addition to the unsaturated system) production can be competing processes. However, the new, mild procedure using catechol borane as the reducing agent seems to circumvent these difficulties. ... 

With electron-deficient aromatic substrates (Entries 4 and 5), high yields and selectivities were observed, but enantioselectivities were variable and solvent-de-pendent (compare Entry 6 with 7 and see Section 1.2.1.3 for further discussion). With a,P-unsaturated tosylhydrazone salts, selectivities and yields were lower. The scope of this process has been extensively mapped out, enabling the optimum disconnection for epoxidation to be chosen [10]. 

Reduction of tosylhydrazones of a, (3-unsaturated ketones by NaBH3CN gives alkenes with the double bond located between the former carbonyl carbon and the a-carbon.280 This reaction is believed to proceed by an initial conjugate reduction, followed by decomposition of the resulting vinylhydrazine to a vinyldiimide. 

Scheme 5.15 shows some examples of the Shapiro reaction. Entry 1 is an example of the standard procedure, as documented in Organic Syntheses. Entry 2 illustrates the preference for the formation of the less-substituted double bond. Entries 3, 4, and 5 involve tosylhydrazone of a, (3-unsaturated ketones. The reactions proceed by a -deprotonation. Entry 6 illustrates the applicability of the reaction to a highly strained system. 

Cyclization of the a,/3-unsaturated JV-tosylhydrazone (94) with carbonate in methanol gives pyrazolophane (95) <79JCR(S)246). 

Many examples of natural furans are recorded as having been prepared from five-membered heterocycles such as 2(5H)-furanones (butenolides), which are reduced to furans with diisobutylaluminum hydride. The facile elimination of selenoxides derived from a-phenylseleneyl-y-lactones with formation of endocyclic a,/3-unsaturated butenolides is reported (75JOC542) as a useful route to 2,4- and 2,3,4-substituted furans via their corresponding butenolides. The mixture of dihydrofurans obtained from the tosylhydrazone of tetrahydro-2-furanone (Scheme 88) was oxidized to furans by 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (66CJC1083). 

Catecholborane is a versatile reducing reagent, a mild and convenient alternative to the classical (Clemmensen, using acids and Wolff-Kishner, using bases) reduction procedure of tosylhydrazones. Regiospecific isomerization occurs during the reduction of a,(3-unsaturated carbonyl derivatives often leading to unique alkenes (Eqs. 134 and 135) 222-223> and allenes (Eq. 136) 224). 

The base catalyzed decomposition of arylsulfonylhydrazones of aldehydes and ketones to provide alkenes is called the Bamford-Stevens reaction. When an organolithium compound is used as the base, the reaction is termed the Shapiro reaction. The most synthetically useful protocol involves treatment of the substrate with at least two equivalents of an organolithium compound (usually MeLi or BuLi) in ether, hexane, or tetramethylenediamine. The in s/ft formed alkenyllithium is then protonated to give the alkene. The above procedure provides good yields of alkenes without side reactions and where there is a choice, the less highly substituted alkene is predominantly formed. Under these reaction conditions tosylhydrazones of a,(3-unsaturated ketones give rise to conjugated dienes. It is also possible to trap the alkenyllithium with electrophiles other than a proton. 

Not all vinylcarbenes will cyclize to the cyclopropene. For example, those with an acyl substituent on the carbene-bearing center preferentially undergo a Wolff rearrangement, but the most significant limitations to the scope of this synthetic route arise from the problems of making the required 3//-pyrazoles. Many routes exist, but as far as cyclopropene synthesis is concerned, the 3/f-pyrazoles have been made (1) by addition of diazoalkanes to alkynes (2) from dihydropyrazoles (3) from cyclization of a,/l-unsaturated tosylhydrazones and finally (4) by modification of the structure of other 37/-pyrazoles. 

Unsaturated ketones, 211-212 a,S-Unsaturated 7-lactones, 200 0,7-Unsaturated methyl sulfinates, 381 a,0-Unsaturated nitriles, 351, 394, 535 0,7-Unsaturated nitriles, 84 a,0-Unsaturated sulfones, 42-43, 436 c ,(3-Unsatutated sulfoxides, 193, 394 a,0-Unsaturated tosylhydrazones, 537 ff, 7-Unsaturated-6 -valerolactones, 188 Uracil, 639, 640... 

Various ot,p y,5-unsaturated 1,3-dipoles are known to undergo 1,7-cyclization by a 871-electrocyclization process (329,330), and the corresponding diazo compounds behave similarly. 5-Diazopenta-l,3-diene derivatives such as 285 (Scheme 8.70), generated in situ by thermolysis of the corresponding tosylhydrazone sodium salts, cyclize to form 1,2-diazepines (286) (331). Sharp and co-workers studied the mechanism, scope, and limitations of this transformation. It was found that cis-substitution about the y,8-double bond prevents the 1,7-cyclization and directs the system toward 1,5-cyclization (332,333) (i.e., formation of a 3//-pyrazole), and that the ot,(3-double bond can be part of a phenyl ring (334). In special cases, the y,8-double bond can be incorporated as part of an aromatic [287 288 (335)] or 2- or 3-thienyl ring as well (336). 

Thermal decomposition of the sodium salts of tosylhydrazones 45a-e gave the triene-conjugated diazo 46a-e, which have a,(3 aromatic and 7, e,C olefinic unsaturation. Such diazo compounds react at 25 °C via an intramolecular [3+2] cycloaddition with unprecedented regioselectivity to give the bridged benzodiazocine 6a-e. 

In situ reduction of tosylhydrazones by NaBHjCN provides an efficient method for the deoxygenation of carbonyl compounds to furnish the corresponding hydrocarbons (see also Section 3.4). In the case of tosylhydrazones derived from a,P-unsaturated carbonyl compounds, the reduction leads to a stereoselective migration of the double bond to give the corresponding tran -alkene. 

In some cases heating the salt of the tosylhydrazone of an a, -unsaturated aldehyde or ketone leads directly to the corresponding carbene but in others it leads to a 3//-pyrazole which can be converted to the carbene and thence the cyclopropene in a separate photochemical step. 

---